The aim is to gain knowledge of the cell membrane-associated contractile and cytoskeletal apparatus, and the differences in organization of this apparatus in normal and in transformed (cancer) cells. Because cytochalasins selectively and reversibly affect this system, in a major part of this study cytochalasins, especially cytochalasin D (CD), will be used as a probe of the membrane-associated contractile structures and their interrelations. The influence of treatments that act in defined ways on cell membrane; on microfilament apparatus and cytoskeletal structures will be studied by examining the structure, filament distribution and 3H-CD uptake of treated cells or fractions, in comparison with the effects of CD. We will especially compare nontransformed and the transformed (including epithelial) cells derived from them with respect to binding of 3H-CD their microfilament apparatus, and the differential effect of CD treatment on their membrane-associated contractile structures and on their behavior. In the ensuing period we propose to examine the actions of cytochalasins and other agents affecting the contractile apparatus in a correlated study using cytoskeletal models, morphologically, immunocytologically and in analytic electropherograms, and the requirements for metabolic energy, protein methylation and Ca ion in induced cell contraction. We will investigate further the differences in arrangement of cytoskeletal structures in paired nontransformed and transformed cells, and their different responses to cytochalasins and related agents. We expect to investigate the basis of the differential cytotoxicity of cytochalasins in 'normal' and cancer cells, and the selective lethality of combined cytochalasin and carcinostatic agents.